Chemotherapy-induced peripheral neurotoxicity(CIPN)is a severe dose-limiting adverse event of chemotherapy.Presently,the mechanism underlying the induction of CIPN remains unclear,and no effective treatment is availab...Chemotherapy-induced peripheral neurotoxicity(CIPN)is a severe dose-limiting adverse event of chemotherapy.Presently,the mechanism underlying the induction of CIPN remains unclear,and no effective treatment is available.In this study,through metabolomics analyses,we found that nab-paclitaxel therapy markedly increased serum serotonin[5-hydroxtryptamine(5-HT)]levels in both cancer patients and mice compared to the respective controls.Furthermore,nab-paclitaxel-treated enterochromaffin(EC)cells showed increased 5-HT synthesis,and serotonin-treated Schwann cells showed damage,as indicated by the activation of CREB3L3/MMP3/FAS signaling.Venlafaxine,an inhibitor of serotonin and norepinephrine reuptake,was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells.Remarkably,venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy.In summary,our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions,and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.展开更多
The overuse of nitrogen(N)fertilizer in fields has increased production costs and raised environmental concerns.Increasing the N use efficiency(NUE)of rice varieties is crucial for sustainable agriculture.Here we repo...The overuse of nitrogen(N)fertilizer in fields has increased production costs and raised environmental concerns.Increasing the N use efficiency(NUE)of rice varieties is crucial for sustainable agriculture.Here we report the cloning and characterization of OsNPF3.1,a gene that controls rice NUE.An amino acid mutation in the OsNPF3.1 coding region caused different NUEs in wild and cultivated rice.OsNPF3.1,which is expressed mainly in the aerial parts of rice,also affects rice plant height,heading date,and thousand-grain weight.The OsNPF3.1 protein is located in the plasma membrane.When OsNPF3.1 was subjected to artificial selection,two naturally varying loci were associated with NUE,of which OsNPF3.1Chr6_8741040differed between indica and japonica rice.OsNPF3.1 can be used as a new target gene for breeding rice varieties with high NUE.展开更多
Background:Horizontal duodenal papilla(HDP)is not an uncommon ectopic major papilla.The impact of HDP on the occurrence of pancreaticobiliary diseases remains unclear.Here,we explored the associations in patients who ...Background:Horizontal duodenal papilla(HDP)is not an uncommon ectopic major papilla.The impact of HDP on the occurrence of pancreaticobiliary diseases remains unclear.Here,we explored the associations in patients who underwent magnetic resonance cholangiopancreatography(MRCP).Methods:Consecutive patients who underwent MRCP at Xijing Hospital(Xi’an,China)between January 2020 and December 2021 were eligible.Patients were divided into HDP and regular papilla(RP)according to the position of the major papilla.The primary out-come was the proportion of congenital pancreaticobiliary diseases.Results:A total of 2,194 patients were included,of whom 72(3.3%)had HDP.Compared with the RP group(n=2,122),the HDP group had a higher proportion of congenital pancreaticobiliary diseases,especially choledochal cyst(CC)or anomalous pancreaticobiliary junction(APBJ)(6.9%vs 1.4%,P=0.001).More gallbladder cancer(6.9%vs 1.2%,P<0.001)and pancreatic cysts(27.8%vs 16.3%,P=0.01)were also identified in the HDP group.Morphologically,the HDP group had a longer extrahepatic bile duct(8.4[7.6-9.3]cm vs 7.2[6.5-8.1]cm,P<0.001),and larger angles between the common bile duct-duodenum and pancreatic duct-duodenum.Multivariate analysis showed that the presence of HDP was an independent risk factor for gallbladder cancer.Conclusions:This study confirmed that HDP was not rare in patients underwent MRCP.A higher prevalence of congenital pancreati-cobiliary malformations(especially CC or APBJ),gallbladder cancer and pancreatic cysts was observed in patients with HDP,as well as distinctive morphologic features.展开更多
基金supported by a Key Project of the Health Bureau of Zhejiang Province(WKJ-ZJ-2325)a Key Project of Zhejiang Provincial Natural Science Foundation(LZ23H160007)+5 种基金the National Natural Science Foundation of China(82373308)Basic Scientific Research Funds of Department of Education of Zhejiang Province(KYYB202212)Zhejiang Province Public Welfare Technology Application Research Project of China(LGF22H160080)Research Project of Zhejiang Provincial People’s Hospital(ZRY2020A005)Basic Scientific Research Funds of the Department of Education of Zhejiang Province(KYQN202128)General Research Projects of Zhejiang Provincial Department of Education(Y202249311).
文摘Chemotherapy-induced peripheral neurotoxicity(CIPN)is a severe dose-limiting adverse event of chemotherapy.Presently,the mechanism underlying the induction of CIPN remains unclear,and no effective treatment is available.In this study,through metabolomics analyses,we found that nab-paclitaxel therapy markedly increased serum serotonin[5-hydroxtryptamine(5-HT)]levels in both cancer patients and mice compared to the respective controls.Furthermore,nab-paclitaxel-treated enterochromaffin(EC)cells showed increased 5-HT synthesis,and serotonin-treated Schwann cells showed damage,as indicated by the activation of CREB3L3/MMP3/FAS signaling.Venlafaxine,an inhibitor of serotonin and norepinephrine reuptake,was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells.Remarkably,venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy.In summary,our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions,and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
基金supported by the National Natural Science Foundation of China(32060476 and 31860371)Guangxi Department of Science and Technology(AA22068087-4)+3 种基金Guangxi Natural Science Foundation of China(2015GXNSFAA139054,2018GXNSFAA138124,and 2020GXNSFAA259041)Guangxi Ministry of Science and Technology(AB21238009)Special Fund of Local Science and Technology Development for the Central Guidance(ZY21195034)Guangxi Academy of Agricultural Sciences(2021JM04,2021JM49,2021YT030,QN-25,and QN-35)。
文摘The overuse of nitrogen(N)fertilizer in fields has increased production costs and raised environmental concerns.Increasing the N use efficiency(NUE)of rice varieties is crucial for sustainable agriculture.Here we report the cloning and characterization of OsNPF3.1,a gene that controls rice NUE.An amino acid mutation in the OsNPF3.1 coding region caused different NUEs in wild and cultivated rice.OsNPF3.1,which is expressed mainly in the aerial parts of rice,also affects rice plant height,heading date,and thousand-grain weight.The OsNPF3.1 protein is located in the plasma membrane.When OsNPF3.1 was subjected to artificial selection,two naturally varying loci were associated with NUE,of which OsNPF3.1Chr6_8741040differed between indica and japonica rice.OsNPF3.1 can be used as a new target gene for breeding rice varieties with high NUE.
基金supported in part by National Key Research and Development Program of China[2022YFC2505100]National Natural Science Foundation of China[No.81970557].
文摘Background:Horizontal duodenal papilla(HDP)is not an uncommon ectopic major papilla.The impact of HDP on the occurrence of pancreaticobiliary diseases remains unclear.Here,we explored the associations in patients who underwent magnetic resonance cholangiopancreatography(MRCP).Methods:Consecutive patients who underwent MRCP at Xijing Hospital(Xi’an,China)between January 2020 and December 2021 were eligible.Patients were divided into HDP and regular papilla(RP)according to the position of the major papilla.The primary out-come was the proportion of congenital pancreaticobiliary diseases.Results:A total of 2,194 patients were included,of whom 72(3.3%)had HDP.Compared with the RP group(n=2,122),the HDP group had a higher proportion of congenital pancreaticobiliary diseases,especially choledochal cyst(CC)or anomalous pancreaticobiliary junction(APBJ)(6.9%vs 1.4%,P=0.001).More gallbladder cancer(6.9%vs 1.2%,P<0.001)and pancreatic cysts(27.8%vs 16.3%,P=0.01)were also identified in the HDP group.Morphologically,the HDP group had a longer extrahepatic bile duct(8.4[7.6-9.3]cm vs 7.2[6.5-8.1]cm,P<0.001),and larger angles between the common bile duct-duodenum and pancreatic duct-duodenum.Multivariate analysis showed that the presence of HDP was an independent risk factor for gallbladder cancer.Conclusions:This study confirmed that HDP was not rare in patients underwent MRCP.A higher prevalence of congenital pancreati-cobiliary malformations(especially CC or APBJ),gallbladder cancer and pancreatic cysts was observed in patients with HDP,as well as distinctive morphologic features.
